SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease
Authors: Eleanor Barnes, Carl S. Goodyear, Michelle Willicombe, Charlotte Gaskell, Stefan Siebert, Thushan I de Silva, Sam M. Murray, Daniel Rea, John A. Snowden, Miles Carroll, Sarah Pirrie, Sarah J. Bowden, Susanna J. Dunachie, Alex Richter, Zixiang Lim, Jack Satsangi, Gordon Cook, Ann Pope, Ana Hughes, Molly Harrison, Sean H. Lim, Paul Miller, Paul Klenerman, Alex G. Richter, Alex Mentzer, Alexandra Deeks, Anni Jamsen, Anthony Brown, Chris Conlon, Chris Dold, Christopher J. A. Duncan, Donal Skelly, Barbara Kronsteiner, Priyanka Abraham, Eloise Phillips, Katie Jeffery, Lance Turtle, Lisa Frending, Lizzie Stafford, Mohammad Ali, Patpong Rongkard, Rebecca Payne, Sandra Adele, Simon Travis, Siobhan Gardiner, Sue L. Dobson, Tom Malone, Sagida Bibi, Miles Carroll, Sian Faustini, Sarah Foulkes, John Frater, Victoria Hall, Susan Hopkins, Jasmin Islam, Teresa Lambe, Stephanie Longet, Shona C. Moore, Ashley Otter, Sarah L. Rowland-Jones, James E. D. Thaventhir, Daniel G. Wootton, Neil Basu, Ashley Gilmour, Sophie Irwin, Georgina Meacham, Thomas Marjot, Stavros Dimitriadis, Peter Kelleher, Maria Prendecki, Candice Clarke, Paige Mortimer, Stacey McIntyre, Rachael Selby, Naomi Meardon, Dung Nguyen, Tom Tipton, Stephanie Longet, Stephen Laidlaw, Kim Orchard, Georgina Ireland, Kevin Brown, Gayatri Amirthalingam, David Thomas, Pamela Kearns, Amanda Kirkham, Iain B. McInnes, Richard Beesley, Vicky Churchill, Holly Loughton, Elspeth Insch, Eilean MacDonald, Gary Middleton, Lucinda Billingham, Faye Lowe, Sophia Magwaro, Saly Al-Taei, Maxine Arnott, Louise Bennett, James Brock, Victora Keillor, Andrew Melville, Lisa Melville, Samantha Miller, Aurelie Najm, Caron Paterson, Lewis Rodgers, Matthew Rutherford, Suzann Rundell, Emily Smith, Lynn Stewart, Flavia Sunzini, Andrew Tong, Kieran Woolcock, Faisal Basheer, Charles Crawley, Ram Malladi, Andrew King, Sophie Lockey, Ben Uttenthal, Mickey B. C. Koh, Sam Hansford, Gurjinder Sandhar, Murali Kesavan, Celia Moore, Pinelopi Manousou, Gareth Hahn, Benjamin Mullish, Maria Atta, Sarah Gleeson, Liz Lightstone, Paul Martin, Stephen McAdoo, Tina Thomson, Daniele Avenoso, Robin Sanderson, Claire Taylor, Khushpreet Bhandal, Diana Hull, Palak Trivedi, Andrew Filer, Erin Hurst, Amy Publicover, Katy Scouse, Jem Chalk, Daniel Hanke, Josef Hanke, Saoirse Healy, Nicholas Provine, Sarah Thomas, Victoria Walker, Zay Win, Doreen Trown, Patricia Faria, Julie Chackathayil, Clare Hutchison, Deborah Richardson
Journal: Nature Medicine (2023)

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (&lt;380 AU ml −1 ). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies.